Probing the role of heterogeneity in streptococcal interactions

项目摘要/摘要 链球菌是人类口腔中最丰富的微生物，大多数人都藏有多发性 物种，甚至经常是同一物种的多个菌株(1-6)。此外，虽然大多数种类的口腔 链球菌不是致病的，对选定菌株的研究表明，链球菌可以影响 牙龈卟啉单胞菌等口腔病原菌的物理定位和毒力因子表达， Aggregatibacter放线菌(AA)和核梭杆菌(2，3，7-11)。这些相互作用 影响疾病的进展和严重程度，以及对治疗的抵抗力(7、12-16)。然而， 这些相互作用也受已知在不同属之间不同的特征所支配，例如细胞表面 结构和分泌的有机酸(17，18)。此外，转录的异质性，这导致 亚群，可以进一步改变微生物的行为(19-23)。因此，虽然丰富的链球菌属 被认为是病原体行为的重要媒介，但目前尚不清楚链球菌- 病原菌的相互作用受到基因组和转录多样性的影响。在本研究中，最重要的是 假说是基因组、表型和转录的异质性影响 共生链球菌和口腔病原体，并影响感染。这笔赠款旨在扩大我们对 通过在基因组和转录两个水平上调查多样性来研究链球菌与病原体的相互作用。第一, 它将系统地描述分类上不同的链球菌与 系统发育框架中的病原体PG和AA(目标1)。这项工作将确定相互作用的规模 在链球菌属中有所不同，并潜在地识别与这些链球菌相互作用的新功能 病原体。其次，这项资助将表征共生链球菌的转录异质性 导致亚群，并询问链球菌和病原体的相互作用如何影响，以及受影响， 亚群(目标2)。这一目标将极大地促进我们对转录的作用的理解 口腔共生链球菌的异质性，它如何在分类学上变化，以及它是如何被环境改变的 改变。此外，这两个目标都将考虑链球菌多样性和空间上的相互作用。 微米级的图案制作。总体而言，这项研究将扩大我们对链球菌作用的理解 在口腔疾病期间。

PROJECT SUMMARY/ABSTRACT Streptococci are the most abundant microbes in the human oral cavity, with most people harboring multiple species, and often even multiple strains of the same species (1-6). Further, while most species of oral streptococci are not pathogenic, studies with selected strains have shown that streptococci can influence the physical location and the virulence factor expression of oral pathogens such as Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), and Fusobacterium nucleatum (2, 3, 7-11). These interactions influence the progression and severity of disease, as well as its resistance to treatment (7, 12-16). However, these interactions also are governed by the traits that are known to vary across the genus, such as cell surface structures and secreted organic acids (17, 18). Further, transcriptional heterogeneity, which results in subpopulations, can further alter the behavior of microbes (19-23). Thus, while the abundant streptococcal genus is thought of as an important mediator of pathogen behavior, it is not well understood how streptococcal- pathogen interactions are impacted by genomic and transcriptomic diversity. In this study, the overarching hypothesis is that genomic, phenotypic, and transcriptional heterogeneity impacts the interactions between commensal streptococci and oral pathogens, and impacts infection. This grant aims to expand our understanding of streptococcal-pathogen interactions by investigating diversity at two levels: genomic and transcriptional. First, it will systematically characterize the interactions formed by taxonomically diverse streptococci with the pathogens Pg and Aa in a phylogenomic framework (Aim 1). This work will identify the scale at which interactions vary across the streptococcal genus and potentially identify new functions that mediate interactions with these pathogens. Second, this grant will characterize the transcriptional heterogeneity in commensal streptococci that result in subpopulations and ask how streptococcal-pathogen interactions influence, and are influenced by, subpopulations (Aim 2). This Aim will significantly advance our understanding of the role of transcriptional heterogeneity in oral commensal streptococci, how it varies taxonomically, and how it is altered by environmental changes. Further, both Aims will consider the interplay of streptococcal diversity and interactions on spatial patterning at the micron-level. Overall, this research will broaden our understanding of the role of streptococci during oral disease.